1. Field of the Invention
This invention relates to surgically implanted mammary prostheses, and in particular pertains to an inflating liquid-gel for mammary prostheses.
2. Description of the Related Art
Mammary prostheses which are implanted surgically generally are made of a silicone medical grade elastomer shell. The prostheses may have added texture to aid in adhesive bonding of the surgically inserted prosthesis to the body tissue. The shell comprises multiple layers of silicone coating and may include an elastomer barrier coat surrounded by the silicone elastomer layer to minimize leakage of inner silicone gel. Mammary prostheses may rupture, both as the result of accidents and when the surrounding shell develops a crease. Such a rupture may be a problem because the integrity and form of the prosthesis is destroyed. Also, the body tissues are exposed to the silicone gel when the prosthesis ruptures.
Attempts to eliminate the problem of leakage of the silicone have included development of more durable shell materials and structures. Tiffany et al. developed a uniformly dispersed lubricating material in saline to reduce the tendency of the shell to crease with resultant failure of the shell (U.S. Pat. No. 4,731,081). The disclosure of this patent and all other patents and publications cited herein is incorporated herein by reference.
The lubricating substance of Tiffany et al. is a solution or suspension of hydrophilic polymer material such as polyvinylpyrrolidone, polyvinyl alcohol, hydroxyethl starch and lecithin, wetting agents such as fatty acid salts or esters, or cottonseed oil or peanut oil. The concentration of the lubricating agent is less than 70% and preferably 5-10% by weight in saline.
Other problems with mammary prostheses include problems with the healing at the surface of the prosthesis. Alterations in texture and addition of surface coverings, such as polyurethane, have not solved the problem, and the latter are believed to cause problem due to toxic or carcinogenic effects.
Applicant herein uses a non-silicone liquid-gel consisting of cross-linked hyaluronan, also recognized as cross-linked hyaluronic acid and hylan (HA,HY). By the term "liquid-gel" herein, Applicant includes viscous liquids or gels of the cross-linked substance. The consistency which is desired determines whether a viscous liquid or a gel of hylan is used in the prosthesis of the invention. Hyaluronic acid (not cross-linked) is a polysaccharide which occurs naturally in chicken combs, vitreous, synovial fluid, skin and human umbilical cords. It is a glycosaminoglycan containing repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid, the monosaccharide units being linked together with beta 1-4 bonds and disaccharide units being linked with beta 1-3 glycoside bonds to form an unbranched, uncrosslinked polysaccharide chain. Hyaluronic acid generally is found as the sodium salt. HA has been found to promote would healing and to minimize scar formation.
To obtain relatively pure HA, animal connective tissue may be extracted with chloroform-water (U.S. Pat. No. 4,141,973 of Balazs). A 10% NaCl solution of the extract is chloroform extracted. The aqueous phase is adjusted to pH 4-5, followed by another chloroform extraction and/or enzyme treatment. The pH of the new aqueous phase is adjusted to 6-7 followed by another chloroform extraction or high speed centrifugation and complete mixing. The new aqueous phase is filter sterilized and then the HA is ethanol and then acetone precipitated. The resultant HA fraction is sterile, pyrogen free, essentially free of proteins, peptides and nucleic acid impurities, non-antigenic, high molecular weight and does not cause an inflammatory reaction.
A number of bacteria, such as Streptococcus pyogenes, Staphylococcus aureus, and Clostridium perfringens, produce hyaluronidases. Bacterial hyaluronidases may be used to extract hyaluronic acid from sources such as tissue.
Elastoviscous solutions of highly purified HA have been used in ophthalmological viscosurgery and in viscosupplementation of joint fluid using elastoviscous hyaluronan solutions, for example, in the treatment of equine traumatic arthritis.
Hyaluronic acid can be extracted from sources such as animal tissue. It can be chemically modified in situ before it is extracted from animal tissue, by treatment of the tissue with a substance which reacts with proteins such as formaldehyde, glutaraldehyde or glyoxal (U.S. Pat. No. 4,713,448 of Balazs et al.). Such a treatment produces a water extract of a modified HA, termed "Hylan" (HY) with a substantially lower protein content per cubic centimeter than in the absence of the treatment. HY can have a very high weight-average molecular weight of 13.times.10.sup.8 or less. A polymer of any desired molecular weight can be obtained by exposure of the HY to compounds or other agent capable of breaking the glucosidic bonds such as hyaluronidase.
In solutions of 0.5% and higher, HY differs significantly from uncrosslinked HA in its physico-chemical and rheological characteristics, which appears to be due to major changes in macromolecular structure, including additional covalent crosslinks introduced during the treatment with a protein crosslinking immobilizing agent as discussed in the '448 patent. The HY modified structure is sufficient to greatly increase the elastic characteristics of solutions of the HY, without any adverse effect on the beneficial HA characteristics, to provide very viscous aqueous solutions, and to allow it to retain its biocompatibility.
The HY may also be treated with divinyl sulfone (DVS) to provide a highly viscous solution in 0.15M NaCl with only 0.15 to 0.40 wt %. This viscosity decreases with shear rate. The HY also has a very long relaxation time. DVS reacts with HA or its salts in aqueous alkaline solutions to form cross-linked gels (U.S. Pat. No. 4,605,691 of Balazs et al.). The gels swell in aqueous environments, with the swelling being dependent on the degree of cross-linking, which can be controlled by changing the HA molecular weight or concentration, the alkali concentration or the HA/DVS ratio. See also U.S. Pat. Nos. 4,582,865 and 4,636,524 of Balazs et al.
Cross-linked forms of hyaluronans, called hylans, may be formed into water-insoluble soft gels for use as viscosurgical implants in the prevention of postoperative adhesions and scar formation. The use of hylan devices is discussed in Balazs et al. (CIBA Foundation Symposium #143, The Biology of Hyaluronan, John Wiley and Sons, Chichester, Sussex, 1988).
For example, hylan gels are effective in diminishing adhesion formation between the tendon and tendon sheath in the toe; in protecting articular cartilage from scuffs during surgery; in facilitating control of tissue movements, visualization during surgery and collection of blood and tissue debris in surgery; and in arthroscopic surgery of the temporomandibular joint (J. Oral Maxillofac. Surg. 47:(161,1989).
It is therefore an object of this invention to provide a mammary prosthesis containing a gel of a biocompatible, non-toxic, non-immunogenic, and non-inflammatory cross-linked HA in an approximately 99% saline solution.
It is a further object of this invention to provide a method of making such a prosthesis.
Other objects and advantages will be more fully apparent from the following disclosure and appended claims.